Fourteen-Day Gemcitabine-Docetaxel Chemotherapy Is Effective and Safer Compared to 21-Day Regimen in Patients with Advanced Soft Tissue and Bone Sarcoma

Abstract

Gemcitabine-docetaxel (G-D) combination is an effective chemotherapy for patients with advanced soft tissue and bone sarcoma, first developed with G administered on days 1 and 8, and D on day 8 every 21 days and later modified to be administered every 14 days in 2012. The 14-day regimen has become increasingly adopted. However, its efficacy and toxicities have not been compared. We identified 161 patients with metastatic or locally advanced soft tissue and bone sarcoma treated with either a 14-day or 21-day regimen within Northern California Kaiser Permanente from 1 January 2017 to 30 July 2020 and compared the outcomes and toxicity profiles of patients treated with the either regimen. Seventy-nine (49%) and 82 (51%) patients received the 14-day and the 21-day regimen, respectively, with similar response rate (22.8% and 15.8%, p = 0.26), median progression-free survival (PFS, 4.0 and 3.2 months, p = 0.15), and median overall survival (OS, 12.6 and 14.7 months, p = 0.55). Subset analysis of the untreated patients (approximately 60% of the entire cohort) as well as the patients with leiomyosarcoma only (approximately 50% of the entire cohort) showed that OS was not significantly different between the two regimens. Febrile neutropenia requiring hospitalization occurred in 10 and one patients (p = 0.006) and intolerance leading to discontinuation of chemotherapy occurred in 12 and two patients (p = 0.006) treated with the 21-day and the 14-day regimens, respectively. CDKN2A deletion/mutation or CDK4 amplification was associated with worse median OS (p = 0.06), while a RB1 deletion/mutation was associated with better median PFS (p = 0.05), and these two genomic alterations were mutually exclusive. Our data demonstrate that, compared to the traditional 21-day G-D regimen, the 14-day G-D regimen is equally effective but safer. In addition, CDKN2A and RB1 pathways play significant role on the outcomes of the patients.

Sex-dependent Prognosis of Patients with Advanced Soft Tissue Sarcoma

“…Our results also appear to be consistent with the findings from the OS data extracted from both TCGA and the MSK-IMPACT datasets showing that male patients had better OS than female patients ( 2, 24 ). The worse prognosis with mutCDKN2A versus wtCDKN2A is consistent with our previous studies ( 5, 25 ). However, to our knowledge, the worse OS with mutRB1 versus wtRB1 and with mutPTEN versus wtPTEN in advanced STS has not been previously reported.…”

Impact of a Virtual Multidisciplinary Sarcoma Case Conference on Treatment Plan and Survival in a Large Integrated Healthcare System

“…In our recent study examining the patients with metastatic or locally advanced STS and bone sarcoma treated with gemcitabine and docetaxel, the median OS was approximately 12-15 months. 21 One of the factors related to the long median OS with our cohort could be that some of the patients had low disease burden and obtained long and durable remission after local therapy (surgical resection, metastatectomy, or stereotactic radiation) without requiring systemic therapy or after the resection of responded locoregionally advanced disease, and another factor could be related to that a majority of patients in our cohort were chemotherapy-naïve. For example, one patient with newly diagnosed metastatic epithelioid hemangioendothelioma of stomach to liver who received gemcitabine-docetaxel chemotherapy with a minor response and went on to have both the primary tumor and liver metastasis resected has remained free of disease for more than 4 years.…”

Prognostic significance of p53, Sox11, and Pax5 co-expression in mantle cell lymphoma

“…Of notice, most studies addressed the prognostic value of p53 expression in MCL using p53 protein instead of mRNA. P53 had post-transcriptional level regulations, such as translation regulation by internal ribosomal entry site (IRES) 28 and protein stability regulation 29 . Thus, there might be inconsistence between p53 expressions at the mRNA level and the protein level.…”